J. Wollborn et al.

COVID-19 increases the risk for the onset of atrial fibrillation in hospitalized patients

Nature Scientific Reports, July 2022; doi.org/10.1038/s41598-022-16113-6


COVID-19 is associated with significant extrapulmonary symptoms. Myocardial involvement has been described for infections with SARS-CoV-2 which may lead to an increase in morbidity and mortality. The objective of our study was to investigate the association of COVID-19 and atrial fibrillation (AF) or atrial flutter (AFl) in hospitalized patients. This retrospective study used electronic medical records to detect patients with COVID-19 and their comorbidities within the Mass General Brigham hospital system. All patients ≥ 18 years who were hospitalized and received a PCR test for SARS-CoV-2 were screened for inclusion as well as patients from a pre-pandemic cohort. We matched on common risk factors for AF and then used multivariable logistic regression to estimate the odds for AF or AFl. Of 78,725 patients eligible for analysis, 11,004 COVID-19 negative patients were matched to 3,090 COVID-19 positive patients and 5005 pre-pandemic patients were matched to 2283 COVID-19 positive patients. After adjusting for demographics and comorbidities, COVID-19 positive patients had 1.19 times the odds (95% CI 1.00, 1.41) of developing AF compared to COVID-19 negative patients and 1.57 times the odds (95% CI 1.23, 2.00) of developing AF compared to pre-pandemic patients. Our study demonstrated an increased risk for AF, directing the attention for improved screening and treatment regimens for the sequelae of COVID-19. While COVID-19 continues to affect many people around the world, AF may be a significant cause for morbidity and mortality. Adequate detection and treatment of AF is essential to reduce the burden of disease.

Yian Xie et al.

Long-term cardiovascular outcomes of COVID-19

Nature Medicine, February 2022; doi.org/10.1038/s41591-022-01689-3


The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.

C. Venter et al.

Erythrocyte, Platelet, Serum Ferritin, and P-Selectin Pathophysiology Implicated in Severe Hypercoagulation and Vascular Complications in COVID-19

Int J Mol Sci, November 2020; doi: 10.3390/ijms21218234


Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regimeF. De Maio et al.

Improved gut microbiota features after the resolution of SARS‑CoV‑2 infection

Gut Pathogens, October 2021; doi.org/10.1186/s13099-021-00459-9



The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the gastrointestinal tract and several studies have shown an alteration of the gut microbiota in hospitalized infected patients. However, long-term data on microbiota changes after recovery are lacking.


We enrolled 30 patients hospitalized for SARS‑CoV‑2-related pneumonia. Their gut microbiota was analyzed within 48 h from the admission and compared with (1) that of other patients admitted for suspected bacterial pneumonia (control group) (2) that obtained from the same subject 6 months after nasopharyngeal swab negativization.


Gut microbiota alpha-diversity increased 6 months after the resolution of SARS-CoV-2 infection. Bacteroidetes relative abundance was higher (≈ 36.8%) in patients with SARS-CoV-2, and declined to 18.7% when SARS-CoV-2 infection resolved (p  =  0.004). Conversely, Firmicutes were prevalent (≈ 75%) in controls and in samples collected after SARS-CoV-2 infection resolution (p  =  0.001). Ruminococcaceae, Lachnospiraceae and Blautia increased after SARS-CoV-2 infection resolution, rebalancing the gut microbiota composition.


SARS-CoV-2 infection is associated with changes in the gut microbiome, which tend to be reversed in long-term period.

D.H. Coelhoet al.

Decreasing Incidence of Chemosensory Changes by COVID-19 Variant

Otolaryngol. Head Neck Surg., May 2022; doi: 10.1177/01945998221097656.


Anedoctal clinical observation suggests that rates of chemosensory dysfunction associated with COVID-19 infection may be decreasing. To investigate, the National COVID Cohort Collaborative database was queried for all patients with and without smell and taste loss within 2 weeks of COVID-19 diagnosis. Six-week periods of peak variant prevalence were selected by using CoVariants.org for analysis. Of 3,678,214 patients with COVID-19 in the database, 616,318 met inclusion criteria during the time intervals of interest, with 3431 having an associated smell or taste disturbance diagnosis. With the initial/untyped variant set as the baseline, the odds ratios for alpha, delta, and omicron (December 27, 2021-February 7, 2022) were 0.50 (95% CI, 0.45-0.55; P < .0001), 0.44 (95% CI, 0.41-0.48; P < .0001), and 0.17 (95% CI, 0.15-0.18; P < .0001), respectively. These data strongly support the clinical observation that patients infected with more recent variants are at a significantly lower risk of developing associated chemosensory loss.

Zazhytska et al.

Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia

Cell Press, February 2022; doi.org/10.1016/j.cell.2022.01.024


SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage in a variety of organs. Thus, deciphering the non-cell-autonomous effects of SARS-CoV-2 infection is imperative for understanding the cellular and molecular disruption it elicits. Neurological and cognitive defects are among the least understood symptoms of COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both in humans and hamsters, SARS-CoV-2 infection causes widespread downregulation of olfactory receptors (ORs) and of their signaling components. This non-cell-autonomous effect is preceded by a dramatic reorganization of the neuronal nuclear architecture, which results in dissipation of genomic compartments harboring OR genes. Our data provide a potential mechanism by which SARS-CoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect, offering insight to its systemic effects in olfaction and beyond.

A. Natarajan et al.

Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection

Med, June 2022 ; doi.org/10.1016/j.medj.2022.04.001


Background: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1, SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2–4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.5

Methods: We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms.

Findings: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%–60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%–18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%–7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.

Conclusions: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19.

I.Katsoularis et al.

Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study

BMJ, April 2022; doi.org/10.1136/bmj-2021-069590


Objective: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.

Design: Self-controlled case series and matched cohort study.

Setting: National registries in Sweden.

Participants: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.

Main outcomes measures: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).

Results: Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.

Conclusions: The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.

S. Tsalamandris et al.

The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives

European Cardiology Review, 2019; doi.org/10.15420/ecr.2018.33.1


Diabetes is a complex metabolic disorder affecting the glucose status of the human body. Chronic hyperglycaemia related to diabetes is associated with end organ failure. The clinical relationship between diabetes and atherosclerotic cardiovascular disease is well established. This makes therapeutic approaches that simultaneously target diabetes and atherosclerotic disease an attractive area for research. The majority of people with diabetes fall into two broad pathogenetic categories, type 1 or type 2 diabetes. The role of obesity, adipose tissue, gut microbiota and pancreatic beta cell function in diabetes are under intensive scrutiny with several clinical trials to have been completed while more are in development. The emerging role of inflammation in both type 1 and type 2 diabetes (T1D and T1D) pathophysiology and associated metabolic disorders, has generated increasing interest in targeting inflammation to improve prevention and control of the disease. After an extensive review of the possible mechanisms that drive the metabolic pattern in T1D and T2D and the inflammatory pathways that are involved, it becomes ever clearer that future research should focus on a model of combined suppression for various inflammatory response pathways.

J. P. Block et al.

Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination - PCORnet, United States, January 2021-January 2022

MMWR,April 2022;  doi: 10.15585/mmwr.mm7114e1


Cardiac complications, particularly myocarditis and pericarditis, have been associated with SARS-CoV-2 (the virus that causes COVID-19) infection (1-3) and mRNA COVID-19 vaccination (2-5). Multisystem inflammatory syndrome (MIS) is a rare but serious complication of SARS-CoV-2 infection with frequent cardiac involvement (6). Using electronic health record (EHR) data from 40 U.S. health care systems during January 1, 2021-January 31, 2022, investigators calculated incidences of cardiac outcomes (myocarditis; myocarditis or pericarditis; and myocarditis, pericarditis, or MIS) among persons aged ≥5 years who had SARS-CoV-2 infection, stratified by sex (male or female) and age group (5-11, 12-17, 18-29, and ≥30 years). Incidences of myocarditis and myocarditis or pericarditis were calculated after first, second, unspecified, or any (first, second, or unspecified) dose of mRNA COVID-19 (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) vaccines, stratified by sex and age group. Risk ratios (RR) were calculated to compare risk for cardiac outcomes after SARS-CoV-2 infection to that after mRNA COVID-19 vaccination. The incidence of cardiac outcomes after mRNA COVID-19 vaccination was highest for males aged 12-17 years after the second vaccine dose; however, within this demographic group, the risk for cardiac outcomes was 1.8-5.6 times as high after SARS-CoV-2 infection than after the second vaccine dose. The risk for cardiac outcomes was likewise significantly higher after SARS-CoV-2 infection than after first, second, or unspecified dose of mRNA COVID-19 vaccination for all other groups by sex and age (RR 2.2-115.2). These findings support continued use of mRNA COVID-19 vaccines among all eligible persons aged ≥5 years.

P. E. Lazzerini et al.

Inflammatory cytokines and cardiac arrhythmias: the lesson from COVID-19

Nat Rev Immunol. 2022; doi: 10.1038/s41577-022-00714-3


Although inflammatory cytokines are implicated in the pathogenesis of cardiac arrhythmias, inflammation is still largely overlooked in the current management of heart rhythm disorders. Now, COVID-19, a systemic inflammatory disease, causes an unexpectedly high prevalence of arrhythmic events, emphasizing the relevance of inflammation in the pathogenesis of cardiac arrhythmias.

Zazhytska M et al

Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia

Cell, https://www.cell.com/cell/fulltext/S0092-8674(22)00135-0

CONTENUTO E COMMENTO: Il deficit olfattivo legato a COVID-19 è un fenomeno tanto ampiamente riconosciuto quanto incompreso nei suoi meccanismi fisiopatologici : in questo studio si osserva che sia nell’uomo che nel criceto l’infezione da SARS-CoV-2 provoca una down-regolazione dei recettori olfattivi, con riorganizzazione dell’architettura del nucleo cellulare del neurone e la perdita della compartimentazione dei geni che codificano per i recettori stessi. In sintesi, il fenomeno dell’iposmia avrebbe origine da un danno che origina fin dalla trascrizione genica.

Gwenaëlle Douaud et al.

SARS-CoV-2 is associated with changes in brain structure in UK Biobank

Nature, https://www.nature.com/articles/s41586-022-04569-5_reference.pdf

CONTENUTO E COMMENTO: In questo studio sono state analizzate le alterazioni cerebrali in 785 pazienti (età 51-81) sottoposti due volte ad imaging cerebrale (pre-pandemia e durante la pandemia), de1 quali 401 casi hanno contratto un’infezione da SARS-CoV-2 tra un esame e l’altro. Sono stati identificati differenze significative confrontando i due gruppi: nei pazienti che hanno contratto l’infezione da Sars-CoV2 si è evidenziata una riduzione dello spessore della corteccia cerebrale e della presa di contrasto nella corteccia orbitofrontale e nella circonvoluzione paraippocampale, alterazioni dei marcatori di danno tissutale nelle regioni funzionalmente collegate alla corteccia olfattiva primaria, e una maggiore atrofia cerebrale. Inoltre coloro che hanno avuto un’infezione da Sars-CoV2 riportavano un maggiore declino cognitivo. Le alterazioni dell’imaging cerebrale limbico possono essere considerati i segni distintivi in vivo di una diffusione degenerativa della malattia attraverso le vie olfattive, di eventi neuroinfiammatori, o della perdita di input sensoriale a causa di anosmia.

Proseguendo il follow-up si potrà determinare se queste alterazioni sono reversibili o se persistono a lungo termine.

Hassler L et al

Potential SARS-CoV-2 kidney infection and paths to injury

Nature Reviews, https://www.nature.com/articles/s41581-022-00551-6

CONTENUTO E COMMENTO : Commento a uno studio basato sullo studio anatomopatologico, perlopiù autoptico, degli effetti di SARS-CoV-2 sul parenchima renale.

Xie Y et al

Risks of mental health outcomes in people with covid-19: cohort study

BMJ, https://www.bmj.com/content/376/bmj-2021-068993

CONTENUTO E COMMENTO : Studio di coorte su oltre 150.000 pazienti sopravvissuti a infezione da SARS-CoV-2 (almeno 30 giorni) a confronto con un gruppo di pazienti senza storia di infezione e a una coorte storica, precedente il periodo pandemico : aumentato rischio di disturbo d’ansia, depressione, disturbi dell’adattamento e utilizzo di psicofarmaci nella coorte COVID-19.

Petersen et al.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme

European Heart Journal, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755397/pdf/ehab914.pdf

CONTENUTO E COMMENTO : In questo studio sono state valutate le funzioni organo-specifiche dopo un'infezione da lieve a moderata da SARS-CoV-2 rispetto ai controlli. I risultati hanno evidenziato che un’infezione lieve-moderata è associata a alterazioni multiorgano subcliniche che riguardano principalmente la funzionalità respiratoria, cardiaca, della coagulazione e renale. Non sono state osservate associazioni con alterazioni cerebrali strutturali, neurocognitive o deterioramento della qualità della vita. Importante è dunque effettuare screening sistematico delle funzionalità organo-specifiche anche dopo un’infezione lieve o moderata da Sars-CoV-2.

Paolo Boscolo Rizzo et al.

COVID-19-related Smell and Taste Impairment with Widespread Diffusion of SARS-CoV-2 Omicron Variant

Medrxiv.org, https://www.medrxiv.org/content/10.1101/2022.02.17.22271116v1.full.pdf

CONTENUTO E COMMENTO: Studio prospettico condotto per stimare la prevalenza della disfunzione chemiosensoriale di olfatto e gusto auto-riferita in una coorte di studio di soggetti che hanno sviluppato COVID-19 in forma da lieve a moderata nel gennaio-febbraio 2022 (periodo di diffusione della variante Omicron) e confrontato con una coorte di pazienti risultati positivi all'infezione da SARS-CoV-2 tra marzo e aprile 2020. Si è dimostrata una riduzione significativa della prevalenza e della gravità della disfunzione olfattiva e gustativa associata a COVID-19 con l'avvento della variante Omicron.

Wadman M et al

A rampage through the body

Science, https://www.science.org/content/article/how-does-coronavirus-kill-clinicians-trace-ferocious-rampage-through-body-brain-toes

CONTENUTO E COMMENTO : Una narrazione del « percorso » di SARS-CoV-2 nell’organismo umano e dei danni provocati nei principali distretti corporei.

Tegan K Boehmer

Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data - United States, March 2020-January 2021

MMWR Morb Mortal Wkly Rep, https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7035e5-H.pdf

CONTENUTO E COMMENTO: Nel periodo compreso tra marzo 2020 e gennaio 2021 si è registrato un rischio di miocardite quasi 16 volte superiore nei pazienti con COVID-19 rispetto ai pazienti non affetti da questa infezione, con variazioni a seconda del sesso (maggiore nei maschi) e dell'età (maggiore tra i bambini e adulti over 50).

Questi risultati sottolineano l'importanza di attuare strategie di prevenzione, tra cui la vaccinazione, per ridurre l'impatto sulla salute pubblica del COVID-19 e delle sue complicazioni associate.

Jansen J et al

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Cell, https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00520-8

CONTENUTO E COMMENTO : Dimostrazione dell’infezione diretta di cellule renali da parte di SARS-CoV-2 tramite l’utilizzo di organoidi, cioè prototipi di rene formati a partire da cellule staminali. In particolare il danno renale consiste nella fibrosi interstiziale, come dimostrato anche nelle autopsie di persone decedute dopo l’infezione da SARS-CoV-2. Considerando la rilevanza della compromissione renale nell’ambito di COVID-19, avere a disposizione modelli per studiare in vivo il fenomeno appare molto significativo.

Belay ED et al.

Multisystem Inflammatory Syndrome in Adults after SARS-CoV-2 infection and COVID-19 vaccination

CID, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab936/6445178

CONTENUTO: La sindrome multi-infiammatoria sistemica (MIS-A) è una rara complicanza dell’infezione da SARS-CoV2. Questo articolo riporta una case series di 20 pazienti che hanno ricevuto diagnosi di MIS-A tra il 14 dicempre 2020 e il 30 aprile 2021. Tutti e 20 i pazienti avevano sviluppato recente infezione da SARS-CoV2, e 7 pazienti (35%) erano stati recentemente sottoposti a vaccinazione. Tuttavia, in considerazione della larga diffusione di soggetti vaccinati, e dalla bassa incidenza di diagnosi di MIS-A, è verosimile che questa rara e grave complicanza non sia correlata con la vaccinazione.

COMMENTO: Come rara complicanza, in associazione con l’infezione da SARS-CoV-2, viene descritta l’occorrenza di Sindrome Multi-Infiammatoria Sistemica (MIS-A) anche nell’adulto. Tutti i 20 pazienti, raccolti in una serie casistica da CDC di Atalanta nel corso della prima ondata di COVID-19, hanno sviluppato questa grave complicanza a circa 1 mese dall’esordio della COVID -19; 7 di questi, vaccinati, dopo circa 10 giorni dalla vaccinazione e 3 fra 1 e 3 settimane dalla seconda dose di vaccino. Data la bassa incidenza, non è stato possibile correlare in questi pazienti la MIS-A come evento avverso Alla vaccinazione o come intrinseco alla COVID-19 anche nell’adulto. La sorveglianza deve tuttavia continuare nella fase dell’epidemia sostenuta dalla variante Delta e dalla vaccinazione progressivamente estesa.

Satterfield BA et al

Cardiac involvement in the long-term implications of COVID-19

Nature Reviews Cardiology, https://www.nature.com/articles/s41569-021-00631-3.pdf

CONTENUTO: Review sulle sequele cardiovascolari da COVID-19, sia in fase acuta che post-acuta. Il danno cardiaco è comune durante la fase acuta di COVID-19, è associato ad outcome peggiori nel breve periodo, la genesi è multifattoriale e le anomalie all’imaging sono comuni indipendentemente dalla gravità della sintomatologia. Tuttavia rimane molto da capire sulla storia naturale della malattia cardiaca nei pazienti con sindrome post-acuta da COVID-19. Non è ancora nota l’eziologia delle diverse manifestazioni cliniche dovute alla presenza di SARS-CoV-2 nei tessuti cardiaci, né la correlazione tra i reperti di imaging, la patologia e l’istologia.

COMMENTO: Ormai è ampiamente acquisito che il cuore e l’apparato cardiovascolare sono colpiti da SARS-CoV-2 attraverso un danno a livello muscolare ed endoteliale che segue all’infiammazione di cui il primum movens è il legame con il recettore ACE-2. Questa bella review cerca di fare chiarezza sulle sequele cardiovascolari che avvengono nel corso di COVID-19 sia nella fase acuta che nel c.d. long COVID-19. Si rimarca in particolare la genesi multifattoriale delle lesioni e che queste sono più gravi nell’acuzie oltrechè una certa disparità tra entità funzionale del danno e ciò che risulta dall’indagine strumentale.


Batil A et al

Brain MRI in SARS-CoV-2 pneumonia patients with newly developed neurological manifestations suggestive of brain involvement

Scientific Reports, https://www.nature.com/articles/s41598-021-00064-5

CONTENUTO : Nel corso della pandemia da SARS-CoV-2 si è assistito ad un aumento della frequenza di manifestazioni neurologiche, incluse quelle del sistema nervoso centrale, nei pazienti con COVID-19, a testimonianza della natura neurotropa di questo virus.In questo studio retrospettivo sono stati inclusi pazienti ricoverati con diagnosi clinico-radiologica di polmonite ed infezione da SARS-CoV-2 confermata con RT-PCR e che avessero effettuato una RM per sintomi neurologici sia focali (63%) che non focali (37%). La RM cerebrale ha mostrato la presenza di lesioni nell’82% dei casi.

COMMENTO: Si tratta di uno studio molto interessante anche se l’elevata percentuale di lesioni alla risonanza magnetica cerebrale deriva dalla selezione della casistica che ha riguardato pazienti con manifestazioni neurologiche. Questo nulla inficia la rilevanza dell’osservazione che conferma come SARS-Cov-2 presenta un tropismo per il sistema nervoso centrale che si palesa in maniera clinicamente evidente nelle forme più gravi di malattia.

Fiore G et al

Case report of cardiogenic shock in COVID-19 myocarditis: peculiarities on diagnosis, histology, and treatment

European Heart Journal – Case reports, https://academic.oup.com/ehjcr/article/5/10/ytab357/6367777

CONTENUTO : Caso clinico di un uomo di 45 anni con miocardite COVID-19 relata, ricoverato in terapia intensiva per shock cardiogeno e trattato con inibitore dell’IL-1 (Anakinra) per 6 mesi, con guarigione e recupero completo della funzionalità biventricolare al follow-up a 8 mesi. Il danno miocardico COVID-19 relato risulta principalmente dovuto alla tempesta citochinica, con lieve infiltrato infiammatorio miocardico e con la formazione di microtrombi di piastrine, nel conteso di una sindrome trombo-infiammatoria ostruttiva del microcircolo.

COMMENTO: Caso clinico di un paziente giovane con miocardite e shock cardiogeno trattato con successo con Anakinra (inibitore IL1) e seguito a lungo termine. Da questa singola segnalazione emerge che: 1) lo shock cardiogeno può insorgere come evento che segue lo sviluppo di miocardite; 2) la miocardite è a sua volta dovuta alla tempesta citochimica che la causa; la Anakinra, che riduce la tempesta citochinica, rappresenta una efficace terapia.

Hendrickson KW et al

The Epidemiology of Acute Respiratory Distress Syndrome Before and After Coronavirus Disease 2019

Critical Care, https://www.criticalcare.theclinics.com/action/showPdf?pii=S0749-0704%2821%2900039-7

CONTENUTO E COMMENTO : Trattazione sulla sindrome da distress respiratorio acuto (ARDS), una entità clinica molto grave e frequente  nelle forme critiche di COVID-19. In attesa di definire meglio le caratteristiche della ARDS associata a COVID-19, gli autori di questa revisione suggeriscono di trattarla in analogia alla ARDS « classica ».

Banoei MM et al

Machine-learning-based COVID-19 mortality prediction model and identification of patients at low and high risk of dying

Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03749-5

CONTENUTO: Studio di machine learning alla ricerca di predittori di mortalità intraospedaliera per COVID-19, includendo comorbidità, caratteristiche cliniche ed esami di laboratorio al momento del ricovero in 250 pazienti: emergono come principali fattori associati a mortalità la coronaropatia, il diabete, l’alterazione dello stato di coscienza, una età superiore a 65 anni, la demenza, valori ematici elevati di proteina C reattiva, protrombina e lattati.

COMMENTO: Studio utile a preparare un planning di grande attenzione terapeutica per i pazienti  con COVID 19 a maggior rischio di morte dentificati attraverso l’algoritmo  dell’ intelligenza artificiale

Boehmer TK, et al.

Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data — United States, March 2020–January 2021

Morbidity and Mortality Weekly Report, https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e5.htm?s_cid=mm7035e5_w

CONTENUTO: Studio sull’incidenza di miocardite in una coorte di 36,005,294 pazienti ospedalizzati e ambulatoriali reclutati tra marzo 2020 e gennaio 2021. In questa popolazione, i pazienti che hanno contratto l’infezione da SARS-CoV2 hanno presentato un rischio 16 volte maggiore di sviluppare miocardite.

COMMENTO: : Lo studio conferma che le infezioni virali rappresentano una causa non rara di miocardite e che l’infezione da SARS-CoV-2 aumenta significativamente questo rischio. La considerazione più importante che lo studio suggerisce è che la vaccinazione, pur associata molto raramente alla miocardite, prevenendo il COVID-19 conferisce un beneficio che largamente supera il rischio anche in riferimento a questa complicazione.

Iroungou BA et al.

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

JAMA, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00475-8/fulltext

CONTENUTO: Studio riportante le caratteristiche clinche e mortalità tra pazienti ricoverati per COVID-19 in Gabon nel periodo intercorrente tra marzo e giugno 2020. In questa popolazione, la mortalità complessiva è risultata del 1.4%, con un’età media complessivamente minore rispetto a quella riportata in altri paesi.

COMMENTO: Le note di importanza di questo studio sono: 1) che lo stato clinico (asintomatico 63%, malattia lieve 34%, malattia grave 3.7%) è associato principalmente all’età e che fattori di rischio sono il sesso maschile e la co-morbidità diabetica; 2) che il basso tasso di letalità (Case Fatality Ratio, CFR) pari a 1.4% è significativamente correlato all’età più avanzata. La composizione giovanile della popolazione africana giustifica il minore impatto (ad es. versus l’AIDS) che la COVID-19 ha in Africa.

Lui L et al.

Mental and neurological disorders and risk of COVID-19 susceptibility, illness severity and mortality: A systematic review, meta-analysis and call for action

 EClinical Medicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00391-6/fulltext

CONTENUTO: Review sistematica esplorante il ruolo dei disordini neuropsichiatrici nel corso della pandemia.  Con il limite di un’elevata eterogeneità degli studi, l’analisi di 149 lavori ha documentato che gli individui affetti da patologie neurologiche o psichiatriche presentano un rischio aumentato sia di contrarre la malattia che di sviluppare un’infezione severa. Questi pazienti presentano inoltre una più elevata mortalità rispetto alla popolazione generale. Tali risultati richiamano all’attenzione la necessità di identificare precocemente tali pazienti per una più efficace gestione dell’impatto della pandemia. Ulteriori ricerche dovranno chiarire i meccanismi patofisiologici alla base di tale associazione.

COMMENTO: Per questo studio l’unico commento aggiuntivo è che l’espressività di malattia grave è più frequente nei pazienti più giovani e che le sequele di turbe mentali sono più frequenti nei pazienti che vivono in regioni a basso o medio-basso reddito. Questi setting devono pertanto essere particolarmente attenzionati.

Patel P et al.

Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults

A Systematic Review

JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784427

CONTENUTO: Revisione sistematica sulla Sindrome Infiammatoria Multisistemica (MIS-A) negli adulti, al fine di riassumerne le caratteristiche cliniche ed epidemiologiche. Su 221 pazienti con MIS-A, i segni e sintomi più frequenti sono stati febbre (96%), ipotensione (60%), disfunzione cardiaca (54%), dispnea (52%) e diarrea (52%). Il 57% dei pazienti ha necessitato di ricovero in terapia intensiva, 47% di supporto respiratorio e il 7% è deceduto. La maggior parte dei pazienti aveva un aumento dei markers di coagulopatia e/o infiammazione e una sierologia positiva per SARS-COV-2. Questi risultati suggeriscono che la MIS-A è una condizione di iperinfiammazione grave che si presenta in media dopo 4 settimane dalla diagnosi di COVID-19 acuta con una disfunzione multi organo extra-polmonare.

COMMENTO:La sindrome infiammatoria multiresistente è piuttosto rara negli adulti essendo più caratteristica dell’età pediatrica. Gli Autori hanno condotto una indagine approfondita interrogando diverse banche dati internazionali. In particolare, in aggiunta a quanto sopra commentato, sottolineo che questa sindrome si verifica in soggetti giovani (età media 21 anni) range 19-34 anni, prevalentemente in pazienti non ispanici neri e senza patologie pregresse.

Deana C et al

Pericardial Cytokine “Storm” in a COVID-19 Patient: the Confirmation of a Hypothesis

Inflammation, https://link.springer.com/article/10.1007/s10753-021-01563-3

CONTENUTO: Caso clinico di un paziente con infezione da SARS-CoV-2 caratterizzata da stato iper-infiammatorio con coinvolgimento isolato del pericardio e tamponamento cardiaco. L’analisi del liquido pericardico ha evidenziato una concentrazione di citochine più alta di quella ematica.

COMMENTO:Esiste un’ampia letteratura che indica come alla base delle forme gravi di malattia, ci siauna tempesta citochinica che produce un danno multi-organo. L’interesse di questa segnalazione su questo singolo caso (che in genere richiederebbe una più ampia casistica di conferma) sta proprio nell’estrema rarità dell’evento – pericardite isolata – in cui è stata dimostrata in modo elegante la presenza di citochine a livello del liquido pericardico.

Wei EK et al

Nine Lessons Learned From the COVID-19 Pandemic for Improving Hospital Care and Health Care Delivery

JAMA, July 2021 ; doi:10.1001/jamainternmed.2021.4237

COMMENTO : New York City (NYC) was the epicenter of the COVID-19 pandemic in the US in March 2020. A dense city of only 302 square miles, it has had 33 359 deaths and 109 192 hospitalizations due to COVID-19 as of June 15, 2021.1 In guiding NYC Health + Hospitals, the largest municipal hospital system in the US, through the pandemic, we have learned a number of lessons. Although there is much to debate about the national public health response to COVID-19,2 we focus on the lessons learned through COVID-19 that we believe have applicability for improving hospital care in the future. The growth of telehealth has been covered elsewhere.3,4 We present 9 other lessons for improving hospital care and health care delivery.

Jassat W et al

Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study

The Lancet, July 2021; doi.org/10.1016/S2214-109X(21)00289-8

COMMENTO : Background

The first wave of COVID-19 in South Africa peaked in July, 2020, and a larger second wave peaked in January, 2021, in which the SARS-CoV-2 501Y.V2 (Beta) lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves.


In this prospective cohort study, we analysed data from the DATCOV national active surveillance system for COVID-19 admissions to hospital from March 5, 2020, to March 27, 2021. The system contained data from all hospitals in South Africa that have admitted a patient with COVID-19. We used incidence risk for admission to hospital and determined cutoff dates to define five wave periods: pre-wave 1, wave 1, post-wave 1, wave 2, and post-wave 2. We compared the characteristics of patients with COVID-19 who were admitted to hospital in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using random-effect multivariable logistic regression.


Peak rates of COVID-19 cases, admissions, and in-hospital deaths in the second wave exceeded rates in the first wave: COVID-19 cases, 240·4 cases per 100 000 people vs 136·0 cases per 100 000 people; admissions, 27·9 admissions per 100 000 people vs 16·1 admissions per 100 000 people; deaths, 8·3 deaths per 100 000 people vs 3·6 deaths per 100 000 people. The weekly average growth rate in hospital admissions was 20% in wave 1 and 43% in wave 2 (ratio of growth rate in wave 2 compared with wave 1 was 1·19, 95% CI 1·18–1·20). Compared with the first wave, individuals admitted to hospital in the second wave were more likely to be age 40–64 years (adjusted odds ratio [aOR] 1·22, 95% CI 1·14–1·31), and older than 65 years (aOR 1·38, 1·25–1·52), compared with younger than 40 years; of Mixed race (aOR 1·21, 1·06–1·38) compared with White race; and admitted in the public sector (aOR 1·65, 1·41–1·92); and less likely to be Black (aOR 0·53, 0·47–0·60) and Indian (aOR 0·77, 0·66–0·91), compared with White; and have a comorbid condition (aOR 0·60, 0·55–0·67). For multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 31% increased risk of in-hospital mortality in the second wave (aOR 1·31, 95% CI 1·28–1·35). In-hospital case-fatality risk increased from 17·7% in weeks of low admission (<3500 admissions) to 26·9% in weeks of very high admission (>8000 admissions; aOR 1·24, 1·17–1·32).


In South Africa, the second wave was associated with higher incidence of COVID-19, more rapid increase in admissions to hospital, and increased in-hospital mortality. Although some of the increased mortality can be explained by admissions in the second wave being more likely in older individuals, in the public sector, and by the increased health system pressure, a residual increase in mortality of patients admitted to hospital could be related to the new Beta lineage.

Estenssoro E et al

Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study

The Lancet, July 2021; doi.org/10.1016/S2213-2600(21)00229-0

COMMENTO : Background : Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country.

Methods : In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete.

Findings : Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52–70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7–22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0–7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8–12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111–218), respiratory system compliance 36 mL/cm H2O (29–44), driving pressure 12 cm H2O (10–14), and FiO2 0·60 (0·45–0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01–1·03]), Charlson score (1·16 [1·11–1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10–1·71]), vasopressor use on day 1 (1·29 [1·07–1·55]), D-dimer concentration (1·02 [1·01–1·03]), PaO2/FiO2 on day 1 (0·998 [0·997–0·999]), arterial pH on day 1 (1·01 [1·00–1·01]), driving pressure on day 1 (1·05 [1·03–1·08]), acute kidney injury (1·66 [1·36–2·03]), and month of admission (1·10 [1·03–1·18]) as independent predictors of mortality.

Interpretation : In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere.

Aschman T et al

Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died

JAMA, June 2021 ; doi:10.1001/jamaneurol.2021.2004

COMMENTO : Importance  Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19.

Objective  To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died.

Design, Setting, and Participants  This case-control autopsy series was conducted in a university hospital as a multidisciplinary postmortem investigation. Patients with COVID-19 or other critical illnesses who had died between March 2020 and February 2021 and on whom an autopsy was performed were included. Individuals for whom informed consent to autopsy was available and the postmortem interval was less than 6 days were randomly selected. Individuals who were infected with SARS-CoV-2 per polymerase chain reaction test results and had clinical features suggestive of COVID-19 were compared with individuals with negative SARS-CoV-2 polymerase chain reaction test results and an absence of clinical features suggestive of COVID-19.

Main Outcomes and Measures  Inflammation of skeletal muscle tissue was assessed by quantification of immune cell infiltrates, expression of major histocompatibility complex (MHC) class I and class II antigens on the sarcolemma, and a blinded evaluation on a visual analog scale ranging from absence of pathology to the most pronounced pathology. Inflammation of cardiac muscles was assessed by quantification of immune cell infiltrates.

Results  Forty-three patients with COVID-19 (median [interquartile range] age, 72 [16] years; 31 men [72%]) and 11 patients with diseases other than COVID-19 (median [interquartile range] age, 71 [5] years; 7 men [64%]) were included. Skeletal muscle samples from the patients who died with COVID-19 showed a higher overall pathology score (mean [SD], 3.4 [1.8] vs 1.5 [1.0]; 95% CI, 0-3; P < .001) and a higher inflammation score (mean [SD], 3.5 [2.1] vs 1.0 [0.6]; 95% CI, 0-4; P < .001). Relevant expression of MHC class I antigens on the sarcolemma was present in 23 of 42 specimens from patients with COVID-19 (55%) and upregulation of MHC class II antigens in 7 of 42 specimens from patients with COVID-19 (17%), but neither were found in any of the controls. Increased numbers of natural killer cells (median [interquartile range], 8 [8] vs 3 [4] cells per 10 high-power fields; 95% CI, 1-10 cells per 10 high-power fields; P < .001) were found. Skeletal muscles showed more inflammatory features than cardiac muscles, and inflammation was most pronounced in patients with COVID-19 with chronic courses. In some muscle specimens, SARS-CoV-2 RNA was detected by reverse transcription–polymerase chain reaction, but no evidence for a direct viral infection of myofibers was found by immunohistochemistry and electron microscopy.

Conclusions and Relevance  In this case-control study of patients who had died with and without COVID-19, most individuals with severe COVID-19 showed signs of myositis ranging from mild to severe. Inflammation of skeletal muscles was associated with the duration of illness and was more pronounced than cardiac inflammation. Detection of viral load was low or negative in most skeletal and cardiac muscles and probably attributable to circulating viral RNA rather than genuine infection of myocytes. This suggests that SARS-CoV-2 may be associated with a postinfectious, immune-mediated myopathy.

Perlis RH et al

Factors Associated With Self-reported Symptoms of Depression Among Adults With and Without a Previous COVID-19 Diagnosis

JAMA, June 2021 ; doi:10.1001/jamanetworkopen.2021.16612

COMMENTO : Rates of major depressive symptoms are elevated after acute infection with SARS-CoV-2. A key question is whether such symptoms represent a general consequence of stress associated with acute illness or whether they reflect more specific sequelae associated with COVID-19 pathophysiology itself. To examine this possibility, in this survey study, we compared features of major depression in individuals with or without prior COVID-19 illness.

Fahmy O et al

Is Microthrombosis the Main Pathology in Coronavirus Disease 2019 Severity?—A Systematic Review of the Postmortem Pathologic Findings

Critical Care Explorations, May 2021; DOI: 10.1097/CCE.0000000000000427

COMMENTO : Objectives: This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019–associated thrombotic pathologies reported in the recent literature.

Data Sources: PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020.

Study Selection: Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019.

Data Extraction: Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death.

Data Synthesis: From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d-dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in non survivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lungvasculaturewere the most common pathologicfindings in the lungs and microthrombi in most of the assessedorgan-tissue.

Conclusions: Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Wide spread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequentpulmonary and extrapulmonarymicrothrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specifichypercoagulability. Furtherdiscovery efforts in assessing the linkbetween coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients isneeded.

Docherty AB et al

Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

The Lancet, May 2021; doi.org/10.1016/S2213-2600(21)00175-2

COMMENTO : Background : Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients whore main at high risk of dying in hospital.

Methods : In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). Weincluded all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-wayde composition mediation analysis using natural effects models to explore associations between week of admission and in-hospitalmortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantify ingpotential mediators (level of respiratory support and steroid treatment). The primaryoutcomewasweekly in-hospital mortality at 28 days, defined as the proportion of patients who haddied within 28 days of admission of all patients admitted in the observedweek, and itwasassessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260.

Findings : Between March 9, and Aug 2, 2020, werecruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjustedweekly in-hospital mortality declined from 32·3% (95% CI 31·8–32·7) in March 9 to April 26, 2020, to 16·4% (15·0–17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65–0·71]). The higher proportions of patients with severe disease and comorbiditi esearlier in the first wave (March and April) than in June and July accounted for 10·2% of thisreduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroidsaccounted for 22·2%, OR 0·95 (0·94–0·95) of the reduction in in-hospitalmortality.

Interpretation : The reduction in in-hospitalmortality in patients with COVID-19 during the first wave in the UK waspartlyaccounted for by changes in the case-mix and illnessseverity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortalityis not explained by thesefactors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.

Sherry HYC et al

Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium

JAMA, May 2021; doi:10.1001/jamanetworkopen.2021.12131

COMMENTO: Importance  The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome.

Objective  To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19.

Design, Setting, and Participants  This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation.

Exposures  Clinically diagnosed or laboratory-confirmed COVID-19.

Main Outcomes and Measures  Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospitalmortality.

Results  Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the meanagewas 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the meanagewas 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reportedneurologicalsymptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The mostprevalentneurologicalsigns and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), whilemeningitis and/or encephalitiswere rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes wasassociatedwithincreasedrisk of in-hospitaldeath (adjustedodds ratio [aOR], 5.99; 95% CI, 4.33-8.28) afteradjusting for study site, age, sex, race, and ethnicity. Presence of preexistingneurologicaldisorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19.

Conclusions and Relevance  In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexistingneurologicaldisorderswereassociatedwithincreasedrisk of developingneurologicalsigns and/or syndromes in COVID-19.

Davogustto GE et al

Characteristics Associated With Multisystem Inflammatory Syndrome Among Adults With SARS-CoV-2 Infection

JAMA, May 2021; doi:10.1001/jamanetworkopen.2021.10323

COMMENTO : A postacute COVID-19 multisystem inflammatory syndrome (MIS) has been recognized as a rare, yet severe, complication of SARS-CoV-2 infection. First characterized in children, MIS in adults (MIS-A) has now been reported, leading to the publication of a working case definition by the Centers for Disease Control and Prevention.

The goal of thiscohortstudywas to describe the spectrum of MIS-A presentationafter SARS-CoV-2 infection. We identified cases of MIS-A among all adults with laboratory-provensubacute or convalescent SARS-CoV-2 infection at a single tertiary care medical center and described their clinica lcharacteristics and outcomes.

Roth G et al

Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic

JAMA, May 2021; doi:10.1001/jamanetworkopen.2021.8828

COMMENTO: Importance  In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted.

Objective  To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics.

Design, Setting, and Participants  This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site.

Main Outcomes and Measures  In-hospital death adjusted for exposures for 4 periods in 2020.

Results  The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73).

Conclusions and Relevance  In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.

Gao M et al

Associations between BMI and COVID-19 severity in 6.9 million people in England: a prospective, community-based, cohort study

The Lancet, April 2021; doi.org/10.1016/S2213-8587(21)00089-9

COMMENTO : Background

Obesityis a major risk factor for adverse outcomes after infection with SARS-CoV-2. We aimed to examine this association, including interactions with demographic and behaviour alcharacteristics, type 2 diabetes, and other health conditions.


In this prospective, community-based, cohort study, we used de-identified patient-level data from the QResearch database of general practices in England, UK. We extracted data for patients aged 20 years and older who were registered at a practice eligible for inclusion in the QResearch database between Jan 24, 2020 (date of the first recorded infection in the UK) and April 30, 2020, and with available data on BMI. Data extracted included demographic, clinical, clinical values linked with Public Health England's database of positive SARS-CoV-2 test results, and death certificates from the Office of National Statistics. Outcomes, as a proxy measure of severe COVID-19, were admission to hospital, admission to an intensive care unit (ICU), and death due to COVID-19. Weused Cox proportional hazard models to estimate the risk of severe COVID-19, sequentially adjusting for demographic characteristics, behaviour alfactors, and comorbidities.


Among 6 910 695 eligible individuals (mean BMI 26·78 kg/m2 [SD 5·59]), 13 503 (0·20%) were admitted to hospital, 1601 (0·02%) to an ICU, and 5479 (0·08%) diedafter a positive test for SARS-CoV-2. We found J-shaped associations between BMI and admission to hospital due to COVID-19 (adjustedhazard ratio [HR] per kg/m2 from the nadir at BMI of 23 kg/m2 of 1·05 [95% CI 1·05–1·05]) and death (1·04 [1·04–1·05]), and a linear association across the whole BMI range with ICU admission (1·10 [1·09–1·10]). Wefound a significant interaction between BMI and age and ethnicity, withhigher HR per kg/m2 above BMI 23 kg/m2 for younger people (adjusted HR per kg/m2 above BMI 23 kg/m2 for hospital admission 1·09 [95% CI 1·08–1·10] in 20–39 yearsage group vs 80–100 years group 1·01 [1·00–1·02]) and Black people than White people (1·07 [1·06–1·08] vs 1·04 [1·04–1·05]). The risk of admission to hospital and ICU due to COVID-19 associated with unit increase in BMI wasslightlylower in people with type 2 diabetes, hypertension, and cardiovascular disease than in those withou tthese morbidities.


At a BMI of more than 23 kg/m2, we found a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which is not attributable to excess risks of related diseases. The relative risk due to increasing BMI isparticularly notable people youngerthan 40 years and of Black ethnicity.


NIHR Oxford BiomedicalResearch Centre.

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Early in the COVID-19 pandemic, obesity was implicated as a clinically significant risk factor for severe disease.1,  2 Multiple studies have supported this theory, and several systematic reviews and meta-analyses on this subject have been published to date.3,  4,  5 However, this association might occur due to a special form of collider bias, termed index event bias.6 Almost all studies of this potential association to date have examined outcomes of patients admitted to hospital and compared progression to intensive care unit (ICU) or death between those with and without obesity. Because either obesity itself or the severity of COVID-19 disease could prompt admission to hospital, the association between these factors might be spurious. A large population-based study, which avoided the risk of collider bias, found that having a body-mass index (BMI) of 30 kg/m2 or higher was associated with a slightly greater risk of death from COVID-19 than a BMI of less than 30 kg/m2.7 However, this study did not examine the risk of unit increases in BMI across the population, of which a large proportion have a BMI lower than 30 kg/m2.

Some studies have found that male gender, some ethnic groups, and people with type 2 diabetes and other chronic conditions might be at higher risk of adverse outcomes from severe SARS-CoV-2 infection.7,  8,  9,  10,  11 Whether these characteristics interact with the effect of excess weight is unclear.

Herewe report results of a large, representative community-based cohortstudy of 6·9 million people in England, UK, to thoroughly characte rise the association between BMI and severe COVID-19 outcomes and to explore interactions with demographic characteristics and other known risk factors.

Wiley Z et al

Racial and Ethnic Differences and Clinical Outcomes of COVID-19 Patients Presenting to the Emergency Department

Clinical Infectious Diseases, April 2021; doi.org/10.1093/cid/ciab290

COMMENTO : Background : Since the introduction of remdesivir and dexamethasone for severe COVID-19 treatment, few large multi-hospital system US studies have describedclinicalcharacteristics and outcomes of minority COVID-19 patients whopresent to the emergency department (ED).

Methods : This cohortstudyfrom the Cerner Real World Database (87 US healthsystems) fromDecember 1, 2019 to September 30, 2020 included PCR-confirmed COVID-19 patients who self-identified as non-Hispanic Black (Black), Hispanic White (Hispanic), or non-Hispanic White (White). The main outcome was hospitalization among ED patients. Secondary outcomes included mechanical ventilation, intensive care unit care, and in-hospitalmortality. Descriptive statistics and Poisson regression compared sociodemographics, comorbidities, receipt of remdesivir, receipt of dexamethasone, and outcomes by racial/ethnic groups and geographicregion.

Results : 94,683 COVID-19 patients presented to the ED. Blacks comprised 26.7% and Hispanics 33.6%. Nearly half (45.1%) of ED patients presented to hospitals in the South. 31.4% (n=29,687) were hospitalized. Lower proportions of Blacks were prescribed dexamethasone (29.4%; n=7,426) compared to Hispanics (40.9%; n=13,021) and Whites (37.5%; n=14,088). Hospitalization risks, compared to Whites, were similar in Blacks (Risk Ratio (RR)=0.94; 95% CI:0.82, 1.08; p=0.4)) and Hispanics RR=0.99 (95% CI:0.81, 1.21; p=0.91), but risk of in-hospital mortality was higher in Blacks, RR=1.18 (95% CI:1.06, 1.31; p=0.002) and Hispanics, RR=1.28 (95% CI: 1.13, 1.44; p < 0.001).

Conclusions : Minority patients were over represented among COVID-19 ED patients, and while they had similar risks of hospitalization as Whites, in-hospitalmortality risk washigher. Interventions targeting upstream social determinants of health are needed to reduce racial/ethnic disparities in COVID-19.

Roubinian NH et al

Incidence of 30-Day Venous Thromboembolism in Adults Tested for SARS-CoV-2 Infection in an Integrated Health Care System in Northern California

JAMA, April 2021, doi:10.1001/jamainternmed.2021.0488

COMMENTO : Hospitalization for COVID-19 isassociatedwith high rates of venousthromboembolism (VTE).1 Whether SARS-CoV-2 infection affects the risk of VTE outside of the hospital setting remainspoorlyunderstood. We report on the 30-day incidence of outpatient and hospital-associated VTE following SARS-CoV-2 testingamongadultmembers of the Kaiser Permanente Northern California health plan.

Tan BK et al

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis

Thorax , February 2021 ; doi.org/10.1136/thoraxjnl-2020-215383

COMMENTO : Background : The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.

Methods : In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020.

Results : We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, pinteraction=0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates.

Conclusions : Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

Leal T et al

Gastrointestinal manifestations of COVID-19: results from a European centre

Journal of Gastroenterology and Hepatology, February 2021 ; DOI: 10.1097/MEG.0000000000002152

COMMENTO : BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce. OBJECTIVES: We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course. METHODS: Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed. RESULTS: Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276). CONCLUSION: A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.

Gallastegui N et al

Pulmonary Embolism Does Not Have an Unusually High Incidence Among Hospitalized COVID19 Patients

Clinical and Applied Thrombosis and Hemostasis, March 2021; doi.org/10.1177/1076029621996471

COMMENTO: INTRODUCTION: Acute respiratory illnesses from COVID19 infection are increasing globally. Reports from earlier in the pandemic suggested that patients hospitalized for COVID19 are at particularly high risk for pulmonary embolism (PE). To estimate the incidences of PE during hospitalization for COVID19, we performed a rigorous systematic review of published literature.

METHODS: We searched for case series, cohort studies and clinical trials from December 1, 2019 to July 13, 2020 that reported the incidence of PE among consecutive patients who were hospitalized for COVID19 in ICUs and in non-ICU hospital wards. To reflect the general population of hospitalized COVID19 patients, we excluded studies in which subject enrollment was linked to the clinical suspicion for venous thromboembolism (VTE).

RESULTS: Fifty-seven studies were included in the analysis. The combined random effects estimate of PE incidence among all hospitalized COVID19 patients was 7.1% (95% CI: 5.2%, 9.1%). Studies with larger sample sizes reported significantly lower PE incidences than smaller studies (r(2) = 0.161, p = 0.036). The PE incidence among studies that included 400 or more patients was 3.0% (95% CI: 1.7%, 4.6%). Among COVID19 patients admitted to ICUs, the combined estimated PE incidence was 13.7% (95% CI: 8.0%, 20.6%). The incidence of ICU-related PE also decreased as the study sample sizes increased. The single largest COVID19 ICU study (n = 2215) disclosed a PE incidence of 2.3% (95% CI: 1.7%, 3.0%). CONCLUSION: PE incidences among hospitalized COVID19 patients are much lower than has been previously postulated based on smaller, often biased study reports. The incidence of "microthrombosis," leading to occlusion of microscopic blood vessels, remains unknown.

Thompson A et al

Cerebral venous sinus thrombosis associated with COVID-19

BMJ, October 2020 ; DOI: 10.1136/practneurol-2020-002678

COMMENTO: Coronavirus disease of 2019 (COVID-19) is well known to increase the risk of developing venous thromboembolism; thus, patients with COVID-19 may present to neurologists with cerebral venous sinus thrombosis. We present a patient presenting acutely with delirium, who after initial negative viral testing, was diagnosed with cerebral venous sinus thrombosis in association with COVID-19.

Hughes C et al

Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19

European Journal of Case Reports in Internal Medicine, April 2020; DOI: 10.12890/2020_001691

COMMENTO: Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the case of a 59-year-old man who presented with headache, hypertension and a single episode of fever with no other symptoms. He subsequently developed unilateral weakness. Computer tomography identified a cerebral venous sinus thrombosis (CVST). A subsequent test for COVID-19 was positive. This is the first report of CVST as a presenting symptom of COVID-19 infection.

Tu TM et al

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review

Journal of Stroke and Cerebrovascular Disease, December 2020;

 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105379

COMMENTO: Background : There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology.

Objective : We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature.

Methods : We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included.

Results : Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%.

Conclusions : The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

Elezkurtaj S et al

Causes of death and comorbidities in hospitalized patients with COVID-19

Scientific Reports, February 2021 ; doi.org/10.1038/s41598-021-82862-5

COMMENTO : Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

Li JY et al

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID‐19 patients: A multicenter retrospective study

Journal of Thrombosis and Haemostasis, February 2021; doi.org/10.1111/jth.15261

COMMENTO : Background : High incidence of asymptomaticvenousthromboembolism (VTE) has been observed in severe COVID‐19 patients, but the characteristics of symptomatic VTE in general COVID‐19 patients have not been described.

Objectives : To comprehensively explore the prevalence and reliable riskprediction for VTE in COVID‐19 patients.

Methods/Results : This retrospective study enrolled all COVID‐19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID‐19. In comparison with 23,434 non‐COVID‐19 medical inpatients, the ORs for developing symptomatic VTE in severe and non‐severe hospitalized COVID‐19 patients were 5.94 (95%CI 3.91 to 10.09) and 2.79 (95%CI 1.43 to 5.60), respectively. When 104 VTE cases and 208 Non‐VTE cases were compared, pulmonary embolism cases had a higher rate for in‐hospital death (OR 6.74, 95%CI 2.18 to 20.81). VTE developed at a median of 21 days (IQR 13.25 to 31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D‐dimer on admission, and D‐dimer increment (DI) ≥ 1.5 fold; of these, DI ≥ 1.5 fold had the most significant association (OR 14.18, 95%CI 6.25–32.18, P = 2.23 × 10‐10). A novel model consisting of simple 3 coagulation variables (fibrinogen and D‐dimer levels on admission, and DI ≥ 1.5 fold) showed good prediction for symptomatic VTE (AUC 0.865, 95%CI 0.822 to 0.907, sensitivity 0.930, specificity 0.710).

Conclusions : There is an excessrisk of VTE in hospitalized COVID‐19 patients. The novel model can help early identification of patients who are at high risk for VTE.

Shah P et al

Is Cardiopulmonary Resuscitation Futile in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest?

Critical Care Medicine, February 2021;  DOI: 10.1097/CCM.0000000000004736

COMMENTO : Objectives: There is limited data regarding outcomes after in-hospital cardiac arrest among coronavirus disease 2019 patients. None of the studies have reported the outcomes of in-hospitalcardiacarrest in coronavirus disease 2019 patients in the United States. Wedescribe the characteristics and outcomes of in-hospitalcardiacarrest in coronavirus disease 2019 patients in rural Southwest Georgia.

Design: Retrospective cohort study.

Setting: Single-center, multihospital.

PATIENTS: Consecutive coronavirus disease 2019 patients who experienced in-hospital cardiac arrest with attempted resuscitation.

Interventions: Attempted resuscitation with advanced cardiac life support.

Measurement and Main Results: Out of 1,094 patients hospitalized for coronavirus disease 2019 during the study period, 63 patients suffered from in-hospital cardiac arrest with attempted resuscitation and were included in this study. The medianage was 66 years, and 49.2% were males. The majority of patients wereAfricanAmericans (90.5%). The most common comorbidities were hypertension (88.9%), obesity (69.8%), diabetes (60.3%), and chronickidneydisease (33.3%). Eighteen patients (28.9%) had a CharlsonComorbidity Index of 0–2. The mostcommonpresentingsymptomswereshortness of breath (63.5%), fever (52.4%), and cough (46%). The median duration of symptomsprior to admission was 14 days. Duringhospital course, 66.7% patients developedsepticshock, and 84.1% had acute respiratorydistress syndrome. Prior to in-hospitalcardiacarrest, 81% were on ventilator, 60.3% were on vasopressors, and 39.7% were on dialysis. The majority of in-hospitalcardiacarrest (84.1%) occurred in the ICU. Time to initiation of advancedcardiac life support protocolwaslessthan 1 minute for all in-hospitalcardiacarrest in the ICU and lessthan 2 minutes for the remaining patients. The most common initial rhythms were pulse less electrical activity (58.7%) and asystole (33.3%). Although return of spontaneous circulation wasachievedin 29% patients, itwas brief in all of them. The in-hospitalmortalitywas 100%.

Connors JM et al

Thrombosis and COVID-19: Controversies and (Tentative) Conclusions

Clinical Infectious Diseases, February 2021 ; doi.org/10.1093/cid/ciab096

COMMENTO: Infection with SARS-CoV-2, initially isolated to one location in early 2020, rapidly spread to become a global pandemic. In early reports, patients with COVID-19 were noted to have multiple coagulation test abnormalities, including elevated D-dimer levels, and increased thrombotic events (1, 2). These complications have been attributed to “thromboinflammation”, a process in which innate immuneresponses and inflammation trigger coagulation, and endotheilialitis (3), a result of infection of endothelial cells with SARS-CoV-2. Severity of inflammation has been associated with extent ofcoagulation test abnormalities: for example, higher IL-6 levels are correlated with increasing fibrinogen levels (4). Autopsy studies, first from China and then from Europe, found microvascularthrombosis in patients with COVID-19; these clots were initially thought to be confined to the lungs but were subsequently found in other organs including the heart and kidneys (1, 5). Microvascular thrombosis may, in turn, lead to hypoxemia, organ failure, and death. The thromboinflammatory response to SARS-COV-2 infection and endothelialitis have been proposed to be driving arterial and venous large vessel thrombosis as well as microvascular thrombosis in people with COVID-19.

Mahase E et al

Covid-19: Sore throat, fatigue, and myalgia are more common with new UK variant

BMJ, January 2021; doi.org/10.1136/bmj.n288 

COMMENTO : People infected with the new variant of covid-19 discovered in the South East of England (known as B.1.1.7 or VUI 202012/01) are more likely to have a cough, sore throat, fatigue, or myalgia than those infected with other variants, the Office for National Statistics has reported.

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